If you think you are at high risk for colon cancer, a simple, painless test could let you know

Colon cancer kills 50,000 Americans annually.

Patients at colon cancer risk — those over 50 or who have a genetic predisposition — currently rely on colonoscopies to look for and remove precancerous growths called polyps.

Doctors at Johns Hopkins have discovered two digestive bacteria that form a film on the colon before polyps appear, raising the prospect that candidates may one day be identified with a simple, painless stool test.

Colon cancer is one of the five most common cancers in men and women in the United States and is also one of the country's leading causes of cancer death. According to the American Cancer Society, an estimated 135,400 people were diagnosed with colon cancer in the United States in 2017, and a little more than 50,260 people succumbed to the disease. One in 22 men and one in 24 women will be diagnosed with colon cancer in their lifetime.

People are used to talking about its potential causes: too much fat, too little fiber, even a rogue gene that can lead to cancer as young as a patient's teens. Now doctors at Johns Hopkins in Baltimore are proposing a new, complementary theory: Many cancers may be traceable to two specific digestive bacteria that form a film on the colon, raising the prospect that some high-risk patients might one day be identified with a simple, painless stool test.

The paper, published last month in the journal Science, says these bacteria invade the protective mucous layer of the colon and create a small ecosystem, including nutrients the bacteria need to survive, causing chronic inflammation and subsequent DNA damage that supports tumor formation.

"It was quite a surprise to find predominantly two bacteria between a [healthy] colon and a precancerous polyp," said Cynthia Sears, an infectious-disease specialist at Johns Hopkins who led the study.

The Hopkins team found these two bacteria — out of more than 500 different classes of bacteria in people's colons and more than a trillion individual bugs in your gut — in patients whose cancers are linked to a genetic syndrome called familial adenomatous polyposis, or FAP.

The bacteria was also linked to patients without a genetic tie to cancer (these cases are known as sporadic cancers). About 95 percent of colon cancer is sporadic. Sears said her research didn't focus on patients who have a different, more common cancer gene, known as HNPCC, or hereditary nonpolyposis colorectal cancer.

The bugs, known as Bacteroides fragilis and Escherichia coli (or E. coli), form a film on the lining of the colon that appears to promote tumor growth, Sears said. In FAP patients the specific B. fragilis strain, called ETBF, produced a toxin that causes colon inflammation. The E. coli strain produced a substance called colibactin, which causes DNA mutations. The combination of the two appears to promote cancer development, Sears said.

"[Sears'] contribution was finding there are two bacteria working together, hand in hand, to enhance cancer," said Christian Jobin, an epidemioligist at the University of Florida in Gainesville.

The question now is what to do about these findings.

A less-invasive way to head off cancer

Eliminating the bacteria isn't possible yet, because antibiotic strategies would likely kill the good bacteria that help make digestion work, said Eric Pamer, director of Memorial Sloan Kettering Cancer Center's Center for Microbiology, Inflammation and Cancer.

More targeted antibiotics could help, and some probiotics might be able to promote other bacteria that would chase the E. coli and ETBF bacteria from the colon, the Johns Hopkins' report said. "You want to hit the 1 percent and leave the 99 percent," Jobin added.

Patients at high risk for colon cancer — those over 50 or who have a genetic predisposition — now rely on colonoscopies to look for and remove precancerous growths called polyps. If further research confirms that bacteria form biofilms on the colon sooner than polyps appear, adding biofilm evaluation or stool analysis could set the stage for less-invasive ways to head off cancer, Sears said.

"We need to know more about these two bacteria, in both people who are healthy and people who develop polyps,'' Sears said. Hopkins is beginning work on a study of 2,000 adults to get a bigger number of colonic biofilms, seeing if the trends her paper noted hold up in a larger population, she said. The National Institutes of Health provided a grant for the study.

"Which bacteria change the gene and how they do it are large questions that remain,'' Sears said.

The American Cancer Society states that there's no sure way to prevent colorectal cancer, but there are things you can do that could help lower your risk, such as maintaining your weight, staying active, not smoking, eating a high-fiber diet and avoiding red meat and processed foods. Jobin from the University of Florida said that fiber and fat levels may affect the development of the EBTF and E. coli bacteria

The research points to a time when doctors have another early-detection tool to keep colon cancers from turning deadly. But the changes on the immediate horizon will be more incremental than fundamental, Pamer said.

"It's going to have an impact but it's not going to be the cure,'' he said. "It's not going to be a huge [innovation] that cuts the risk of cancer by 80 percent.''

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